Cancer is a significant cause of illness-related deaths in the United States. A common therapy for cancer is surgical resection of the tumor, followed by radiation, chemotherapy, or both radiation and chemotherapy. The goal of these therapies is to remove the observable tumor itself and as much additional surrounding tissue as possible in order to decrease the likelihood that pre-neoplastic or neoplastic cells that appear morphologically normal remain in the subject that can later form the basis of a recurrence or metastasis.
In many cases, however, there is a desire to limit the removal of surrounding tissue to the greatest extent possible in order to maintain the appearance and/or function of the tissue from which the tumor was resected. In order to balance the desire to remove potentially neoplastic tissue while preserving normal tissue, the surgeon will often be supported by a pathologist, who during or subsequent to the resection procedure examines the excised tissue. The pathologist's examination is designed to determine if a sufficient boundary of normal tissue surrounding the tumor has been removed to suggest that any potentially neoplastic cells have been resected. This examination of the tumor margin also can be used to determine whether further surgical intervention is necessary.
One situation where the interplay between the desire to completely remove a tumor and yet to minimize the removal of normal tissue is prominent is in breast cancer. It is estimated that about 125,000 women diagnosed with early stage breast cancer receive breast conserving surgery (BCS) each year. BCS involves removal of the cancer with a surrounding margin of normal breast tissue. An important predictor of local recurrence after BCT is pathologic margin status. Reported rates of re-excision surgery as a result of close or positive surgical margins are high (10-40%). Intraoperative frozen section and touch prep cytology have been developed to assess surgical margins and guide additional resection at the time of the initial operation. However, these techniques have not been widely adopted because of the need for specially trained personnel (pathologist), prolonged surgical time required for specimen processing (20-40 minutes), significant technical challenges, and limited coverage of the tumor margins (less than 1% of the margins are examined).
At least in part because of these limitations, re-excision of the tumor site is frequently required. To decrease the need for re-excision, several intra operative techniques have been developed to assess surgical margins and guide additional resection at the time of the initial operation. These methods include intra operative frozen section and touch prep cytology. Among the drawbacks of these techniques are the need for specially trained personnel (pathologist), prolonged surgical time required for specimen processing (2040 minutes), technical problems related to freezing and cutting tissue with high fat content, and limited surveillance of the tumor margins. Moreover, pathological margin assessment relies on visual inspection of the specimen and is unreliable for grossly occult lesions such as DCIS or invasive lobular carcinoma. Thus, these methods have not been widely adopted for intra operative assessment of margins.
What are needed, then, are robust, reliable, and rapid strategies for assessing tumor margins. To address this need, at least in part, the subject matter described herein provides methods and systems for imaging biological samples.